Project Summary Genetic susceptibility contributes significantly to the development of diabetes and its complications. Recent successes in genome wide association and exome sequencing have demonstrated that the technological capability now exists to identify many of the genes responsible for complex disorders. To be successful in such endeavors, it is necessary to combine expertise in genetic epidemiology, clinical investigation, molecular genotyping, DNA sequencing, and mathematical genetic analysis. The goal of the Human Genetics Core is to offer such expertise to DRC investigators conducting genetic studies. To achieve this objective, the Human Genetics Core will: a) Assist DRC investigators in the development and successful completion of well-designed genetic studies; b) Establish and store EBV-transformed lymphoblastoid cell lines (LCLs), as well as PAXgene tubes; c) Provide access to molecular methodology for genome-wide association studies (GWAS) and specialized (e.g., the exome chip) single nucleotide polymorphism (SNP) testing, candidate gene sequencing, whole exome sequencing (WES), whole genome sequencing (WGS), and large-scale gene methylation analysis (by chip); d) Assist with mathematical genetic epidemiologic analysis, including analysis of multi-omics data; e) Make induced pluripotent stem cells (iPSCs), as well as diabetes-relevant cells derived from them, available to investigators as a means of investigating the impact of specific genetic variants on organ development and tissue function; f) Provide training in genetic techniques to DRC investigators and staff; g) Provide a national multi-ethnic (including high-risk minorities) genomics resource for the study of diabete-related phenotypes. In the last cycle, the Human Genetics Core brought GWAS technology to DRC investigators and in this cycle extends the technology available for studying human samples with the addition of specialized genotyping chips, methylation chips, exome and whole genome sequencing, and iPSC technology. The DRC offers a unique opportunity to facilitate research directed at identifying and characterizing the genes responsible for diabetes and related disorders, including both macrovascular and microvascular complications, by providing access to both the expertise and facilities necessary for such genetic research in human populations. In the last cycle, the Human Genetics Core augmented GWAS technology by offering specialized genotyping chips to DRC investigators as well as iPSC technology. In this cycle, the Core will expand the available technologies, including several new specialized genotyping chips (e.g., MegaChip, 850K methylation), next generation sequencing, and diabetes-relevant tissues derived from iPSCs, complemented by updated analysis methods for multi-omic datasets. The DRC offers a unique opportunity to facilitate research directed at identifying and characterizing the genes responsible for diabetes and related disorders by providing access to both the expertise and facilities necessary for such genetic research in human populations.